Pancreatic carcinoma is associated with a high frequency of thrombosis. Most patients with thrombotic disease have a defective fibrinolytic defense system caused either by plasminogen activator deficiency, excess of plasminogen activator inhibitor (PAI-1), or a combination of the two. In the current series of 27 patients with pancreatic carcinoma, 17 had had deep vein thrombosis (DVT) since the onset of their malignant disease, and most were found to have high plasma concentrations of PAI-1 antigen and PAI-1 activity. Analysis of singleton samples from each patient yielded no correlation between previous DVT and currently high plasma PAI-1 concentrations. However, serial samples from 14 patients (8 of whom had histories of thrombosis) showed individual values varied sharply with time, with intermittent peaks both in PAI-1 antigen and PAI-1 activity for 11 of the 14 patients. Such variability may contribute to intermittently excessive hypercoagulability because of a relative reduction in fibrinolytic potential. These changes may predispose the patient to have thrombotic events in association with pancreatic carcinoma.